Effect of enzyme inducers and inhibitors and glutathione precursor and depleter on induced acute aflatoxicosis in rabbits.
Male New Zealand White rabbits were treated with microsomal enzyme inducers, inhibitors of hemoprotein synthesis or action, and glutathione precursor and depletor before they were orally given the median lethal dose (LD50) of aflatoxin B1 (AFB1; 0.4 mg/kg) at the start of a 7-day experimental period. The drugs administered, mean duration of illness (hours), and survival percentage were as follows: controls (saline solution)-85, 50%; phenobarbital (PB)-100, 100%; phenylbutazone-115, 67%; benzoflavone-39, 17%; stanozolol-67, 67%; cobaltous chloride (CoCl2)-46, 67%; piperonyl butoxide (PBO)-88, 100% cysteine (CYS)-68, 100%; ethyl maleate-71, 83%. Signs of toxicosis included decreased feed and water consumption, weight loss, dehydration, lethargy, and emaciation; some rabbits died or were euthanatized. Clinico-pathologic changes included increased serum aspartate aminotransferase (AST) activity by 24 hours and bilirubin concentration by 48 to 72 hours after AFB1 was given. Grossly, livers were pale or tan and friable, with prominent lobular architecture. Kidneys of affected rabbits were pale to dark red. Microscopically, livers were normal or had lesions as great as extensive necrosis, hemorrhage, mineralization, and bile duct proliferation. Treatment of rabbits with PB, CoCl2, PBO, and CYS protected against AFB1 hepatic pathology, and PB, PBO, and CYS also had protective effect against lethality. Ethyl maleate provided some protection against lethality and increased serum AST activity and bilirubin concentration. Toxicosis was enhanced by benzoflavone; phenylbutazone and stanozolol had litte influence.
D000208:Acute Disease; D016604:Aflatoxin B1; D000818:Animals; D001571:Benzoflavones / Q000627:therapeutic use; D002273:Carcinogens; D002712:Chlorides / Q000627:therapeutic use; D003035:Cobalt / Q000627:therapeutic use; D003545:Cysteine / Q000627:therapeutic use; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism*; D006041:Goats; D008099:Liver / Q000473:pathology; D008297:Male; D008298:Maleates / Q000627:therapeutic use; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000627:therapeutic use; D010653:Phenylbutazone / Q000627:therapeutic use; D010882:Piperonyl Butoxide / Q000627:therapeutic use; D011817:Rabbits; D051381:Rats; D013197:Stanozolol / Q000627:therapeutic use; D000096702:Aflatoxin Poisoning
D016604:Aflatoxin B1; D001571:Benzoflavones; D002273:Carcinogens; D002712:Chlorides; D003035:Cobalt; D003545:Cysteine; D004791:Enzyme Inhibitors; D005978:Glutathione; D008298:Maleates; D010634:Phenobarbital; D010653:Phenylbutazone; D010882:Piperonyl Butoxide; D013197:Stanozolol; C014476:diethyl maleate